rs1199610913

Variant names:

• chr19-507766-C-A
• rs1199610913
• NM_033513.3:c.260C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-507766-C-A
• chr19-507766-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033513.3(TPGS1):​c.260C>A​(p.Pro87His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P87L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPGS1 NM_033513.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889
• Publications: 0 publications found

Genes affected

TPGS1 (HGNC:25058): (tubulin polyglutamylase complex subunit 1) Predicted to enable microtubule binding activity. Predicted to be involved in protein polyglutamylation. Predicted to act upstream of or within several processes, including adult behavior; chemical synaptic transmission; and sperm axoneme assembly. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

MADCAM1-AS1 (HGNC:55315): (MADCAM1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15851068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033513.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPGS1	NM_033513.3	MANE Select	c.260C>A	p.Pro87His	missense	Exon 1 of 2	NP_277048.2	Q6ZTW0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPGS1	ENST00000359315.6	TSL:1 MANE Select	c.260C>A	p.Pro87His	missense	Exon 1 of 2	ENSP00000352265.4	Q6ZTW0-1
	TPGS1	ENST00000588278.1	TSL:6	n.267C>A		non_coding_transcript_exon	Exon 1 of 1
	MADCAM1-AS1	ENST00000592413.2	TSL:5	n.68G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 37206 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1241188 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 604668

African (AFR) AF: 0.00 AC: 0 AN: 24510

American (AMR) AF: 0.00 AC: 0 AN: 13288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18502

East Asian (EAS) AF: 0.00 AC: 0 AN: 27988

South Asian (SAS) AF: 0.00 AC: 0 AN: 58588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4548

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1008130

Other (OTH) AF: 0.00 AC: 0 AN: 50702

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.89
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.046
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.32	B
Vest4		0.24
MutPred		0.26		Loss of glycosylation at P87 (P = 0.021)
MVP		0.53
MPC		2.1
ClinPred		0.94	D
GERP RS		4.3
PromoterAI		-0.039	Neutral
Varity_R		0.31
gMVP		0.18
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1199610913; hg19: chr19-507766;